Project Summary ? Overall Nonhuman primates (NHPs) have historically served as crucial animal models for diseases, and for testing of new therapies and vaccines that cannot be evaluated in small animal models. The utility of NHP models in research has been enhanced considerably by the use of immune cell depleting antibodies that can target and lyse specific cell subsets in vivo. In models of infectious disease and vaccine testing, targeted immune cell depletion has been used understand the pathogenesis of these infections and to design better vaccines to prevent them. Furthermore, cell depletion can be an effective immune modulating therapy and the preclinical testing of these cell-depleting antibody drugs is often conducted in nonhuman primates. For the past 18 years, NIH has supported the Nonhuman Primate Reagent Resource?s efforts to develop, characterize, manufacture and distribute immune cell depleting antibodies for use NHP models through a R24 grant. Need for this program has been confirmed by year-over-year growth in program activity since its inception. Over the past year, this grant fulfilled over 125 requests for cell-depleting antibody reagents, supporting at least 50 different NIH grants or programs. Nearly 400 grams of cell-depleting antibody for administration to NHP was distributed. This grant proposes to continue this program providing immune cell depleting antibodies for use in NHPs by maintaining the large-scale manufacture and quality control of the immune cell-depleting and control antibodies. We will also develop antibodies against new targets and improve existing antibodies by engineering for more efficient depletion. Our web-based infrastructure will be used for advertising reagents, receiving and fulfilling requests, and measuring program effectiveness. Efforts to enhance rigor and transparency to improve reproducibility will be accomplished by facilitating the authentication of key biological resources. Finally, we will conduct applied research to enhance effector function of cell-depleting antibodies by exploring way to improve cytotoxicity.